A tragic consequence of passive, or "secondhand," exposure to nicotine is the potential impairment of brain development in infants. Neonatal exposure to nicotine can result in children with diminished auditory function and auditory-related language and cognitive deficits. The long term goal of this research is to understand how exposure to nicotine during development impairs auditory cortex function. Recent studies have shown that rapid activation of alpha-7 nicotinic acetylcholine receptors (alpha-7 nAChRs) in developing auditory cortex selectively enhances synaptic potentials mediated by N?methyl-D-aspartate glutamate receptors (NMDARs). This interaction is vulnerable to the effects of exogenous nicotine, and preliminary data indicate that exposure to nicotine at levels found in the bloodstream of smokers selectively affects NMDAR synaptic activity in the developing cortex. The proposed experiments will test the hypothesis that during development, alpha-7 nAChRs regulate glutamate release at pure-NMDAR synapses (synapses that have only NMDARs postsynaptically). These pure-NMDAR synapses convey sensory inputs to auditory cortex. The experiments use a newly-developed brain slice preparation that maintains a functional pathway conveying thalamic information to auditory cortex. Intracellular (whole-cell patch) recordings in the auditory thalamocortical slice and in the intact animal during acoustic stimulation will be used to determine if: (1) alpha-7 nAChRs regulate thalamocortical synapses during development, (2) presynaptic alpha-7 nAChRs regulate pure-NMDAR synapses, (3) chronic exposure to nicotine during development alters glutamate release at pure-NMDAR synapses, and (4) chronic exposure to nicotine during development impairs sensory function in the adult. Achieving these aims will contribute to an understanding of developmental mechanisms in sensory cortex, and how development can be disrupted by exposure to nicotine.